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Published in: International Journal of Hematology 2/2018

01-02-2018 | Original Article

Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in adult patients with acute lymphoblastic leukemia: clinical outcome and cost-effectiveness analysis

Authors: Yan Wang, Yuanming Xing, Lu Chen, Ti Meng, Ying Li, Jiao Xie, Limei Chen, Yalin Dong, Weihua Dong

Published in: International Journal of Hematology | Issue 2/2018

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Abstract

This study evaluated the clinical and cost-effectiveness of prophylactic use of fluconazole versus mould-active triazoles (voriconazole and posaconazole) in adult patients with acute lymphoblastic leukemia (ALL). A decision analytical model was developed with inputs from a 7-year retrospective study (2009–2016) of 103 consecutive adult patients with ALL who received antifungal prophylaxis. Information on the administration of antifungal agents, clinical outcomes, and costs were collected. One-way sensitivity analyses and probabilistic sensitivity analysis were performed. The mould-active triazoles group was associated with higher life-years (3.71 vs 3.59) and lower total costs (US$4886 vs US$5722) per patient compared with fluconazole. One-way sensitivity analyses revealed that varying all of the key variables in the model did not affect the robustness of the results. Probabilistic sensitivity analysis demonstrated that mould-active triazoles had a probability of 77.1 and 90.1% of providing a dominant and cost-effective option relative to fluconazole, respectively. Mould-active triazoles should be regarded as preferable to fluconazole as the first-line prophylactic for adult patients with ALL accompanied by uncommon severe vinca alkaloid-induced neurotoxicity. However, the results reported here should be interpreted with caution owing to the observational nature of the data.
Literature
1.
go back to reference Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91:986–9.PubMed Chamilos G, Luna M, Lewis RE, Bodey GP, Chemaly R, Tarrand JJ, et al. Invasive fungal infections in patients with hematologic malignancies in a tertiary care cancer center: an autopsy study over a 15-year period (1989–2003). Haematologica. 2006;91:986–9.PubMed
2.
go back to reference Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.PubMed Pagano L, Caira M, Candoni A, Offidani M, Fianchi L, Martino B, et al. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study. Haematologica. 2006;91:1068–75.PubMed
4.
go back to reference Pagano L, Busca A, Candoni A, Cattaneo C, Cesaro S, Fanci R, et al. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. Blood Rev. 2017;31:17–29.CrossRefPubMed Pagano L, Busca A, Candoni A, Cattaneo C, Cesaro S, Fanci R, et al. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations. Blood Rev. 2017;31:17–29.CrossRefPubMed
5.
go back to reference Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32:358–66.CrossRefPubMed Lin SJ, Schranz J, Teutsch SM. Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis. 2001;32:358–66.CrossRefPubMed
6.
go back to reference Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.CrossRefPubMed Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347:408–15.CrossRefPubMed
7.
go back to reference Ananda-Rajah MR, Cheng A, Morrissey CO, Spelman T, Dooley M, Neville AM, et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother. 2011;55:1953–60.CrossRefPubMedPubMedCentral Ananda-Rajah MR, Cheng A, Morrissey CO, Spelman T, Dooley M, Neville AM, et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother. 2011;55:1953–60.CrossRefPubMedPubMedCentral
8.
go back to reference NCCN Guidelines Version 2.2016 of Acute Lymphoblastic Leukemia [Internet]. American: National Comprehensive Cancer Network. http://www.nccn.org/. Accessed 20 Sept 2016. NCCN Guidelines Version 2.2016 of Acute Lymphoblastic Leukemia [Internet]. American: National Comprehensive Cancer Network. http://​www.​nccn.​org/​. Accessed 20 Sept 2016.
9.
go back to reference Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev. 2006;19:435–47.CrossRefPubMedPubMedCentral Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Clin Microbiol Rev. 2006;19:435–47.CrossRefPubMedPubMedCentral
11.
go back to reference Doan TN, Kirkpatrick CMJ, Walker P, Slavin MA, Ananda-Rajah MR, Morrissey CO, et al. Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit. J Antimicrob Chemother. 2016;71:497–505.CrossRefPubMed Doan TN, Kirkpatrick CMJ, Walker P, Slavin MA, Ananda-Rajah MR, Morrissey CO, et al. Primary antifungal prophylaxis in adult patients with acute lymphoblastic leukaemia: a multicentre audit. J Antimicrob Chemother. 2016;71:497–505.CrossRefPubMed
12.
go back to reference Sun Y, Huang H, Chen J, Li J, Ma J, Li J, et al. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol. 2015;36:757–67.CrossRefPubMed Sun Y, Huang H, Chen J, Li J, Ma J, Li J, et al. Invasive fungal infection in patients receiving chemotherapy for hematological malignancy: a multicenter, prospective, observational study in China. Tumour Biol. 2015;36:757–67.CrossRefPubMed
13.
go back to reference Pfizer Inc. Vfend (voriconazole) package insert. New York; 2008. Pfizer Inc. Vfend (voriconazole) package insert. New York; 2008.
14.
go back to reference Merck Inc. Noxafil (posaconazole) package insert. Darmstadt; 2012. Merck Inc. Noxafil (posaconazole) package insert. Darmstadt; 2012.
15.
go back to reference Bohme A, Just-Nubling G, Bergmann L, Shah PM, Stille W, Hoelzer D. Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies. J Antimicrob Chemother. 1996;38:953–61.CrossRefPubMed Bohme A, Just-Nubling G, Bergmann L, Shah PM, Stille W, Hoelzer D. Itraconazole for prophylaxis of systemic mycoses in neutropenic patients with haematological malignancies. J Antimicrob Chemother. 1996;38:953–61.CrossRefPubMed
16.
go back to reference Niwa T, Imagawa Y, Yamazaki H. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr Drug Metab. 2014;15:651–79.CrossRefPubMed Niwa T, Imagawa Y, Yamazaki H. Drug interactions between nine antifungal agents and drugs metabolized by human cytochromes P450. Curr Drug Metab. 2014;15:651–79.CrossRefPubMed
17.
go back to reference Al-Badriyeh D, Slavin M, Liew D, Thursky K, Downey M, Grigg A, et al. Pharmacoeconomic evaluation of voriconazole versus posaconazole for antifungal prophylaxis in acute myeloid leukaemia. J Antimicrob Chemother. 2010;65:1052–61.CrossRefPubMed Al-Badriyeh D, Slavin M, Liew D, Thursky K, Downey M, Grigg A, et al. Pharmacoeconomic evaluation of voriconazole versus posaconazole for antifungal prophylaxis in acute myeloid leukaemia. J Antimicrob Chemother. 2010;65:1052–61.CrossRefPubMed
18.
go back to reference Grau S, de la Camara R, Sabater FJ, Jarque I, Carreras E, Casado MA, et al. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain. BMC Infect Dis. 2012;12:83.CrossRefPubMedPubMedCentral Grau S, de la Camara R, Sabater FJ, Jarque I, Carreras E, Casado MA, et al. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain. BMC Infect Dis. 2012;12:83.CrossRefPubMedPubMedCentral
19.
go back to reference Heng SC, Slavin MA, Al-Badriyeh D, Kirsa S, Seymour JF, Grigg A, et al. Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy. J Antimicrob Chemother. 2013;68:1669–78.CrossRefPubMed Heng SC, Slavin MA, Al-Badriyeh D, Kirsa S, Seymour JF, Grigg A, et al. Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy. J Antimicrob Chemother. 2013;68:1669–78.CrossRefPubMed
20.
go back to reference Mauskopf J, Chirila C, Graham J, Gersten ID, Leather H, Maziarz RT, et al. Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. Am J Health Syst Pharm. 2013;70:1518–27.CrossRefPubMedPubMedCentral Mauskopf J, Chirila C, Graham J, Gersten ID, Leather H, Maziarz RT, et al. Comparative cost-effectiveness analysis of voriconazole and fluconazole for prevention of invasive fungal infection in patients receiving allogeneic hematopoietic cell transplants. Am J Health Syst Pharm. 2013;70:1518–27.CrossRefPubMedPubMedCentral
21.
go back to reference Zhao YJ, Khoo AL, Tan G, Teng M, Tee C, Tan BH, et al. Network meta-analysis and pharmacoeconomic evaluation of fluconazole, itraconazole, posaconazole, and voriconazole in invasive fungal infection prophylaxis. Antimicrob Agents Chemother. 2016;60:376–86.CrossRef Zhao YJ, Khoo AL, Tan G, Teng M, Tee C, Tan BH, et al. Network meta-analysis and pharmacoeconomic evaluation of fluconazole, itraconazole, posaconazole, and voriconazole in invasive fungal infection prophylaxis. Antimicrob Agents Chemother. 2016;60:376–86.CrossRef
22.
go back to reference De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.CrossRefPubMedPubMedCentral De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46:1813–21.CrossRefPubMedPubMedCentral
23.
go back to reference National Health and Family Planning Commission of the People’s Republic of China. Chinese Statistical Yearbook of Health and Family Planning of 2015. Beijing: Peking Union Medical University; 2015. National Health and Family Planning Commission of the People’s Republic of China. Chinese Statistical Yearbook of Health and Family Planning of 2015. Beijing: Peking Union Medical University; 2015.
25.
go back to reference Lewis G, Hall P, Eisa N, Deremer D, Dobbins R, El-Geneidy M, et al. Acute myelogenous leukemia patients are at low risk for invasive fungal infections after high-dose cytarabine consolidations and thus do not require prophylaxis. Acta Haematol. 2010;124:206–13.CrossRefPubMed Lewis G, Hall P, Eisa N, Deremer D, Dobbins R, El-Geneidy M, et al. Acute myelogenous leukemia patients are at low risk for invasive fungal infections after high-dose cytarabine consolidations and thus do not require prophylaxis. Acta Haematol. 2010;124:206–13.CrossRefPubMed
26.
go back to reference Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.CrossRefPubMed Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007;356:348–59.CrossRefPubMed
27.
go back to reference Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007;356:335–47.CrossRefPubMed Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007;356:335–47.CrossRefPubMed
28.
go back to reference Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden LR, et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116:5111–8.CrossRefPubMedPubMedCentral Wingard JR, Carter SL, Walsh TJ, Kurtzberg J, Small TN, Baden LR, et al. Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. Blood. 2010;116:5111–8.CrossRefPubMedPubMedCentral
29.
go back to reference Sculpher MJ, Claxton K, Drummond M, McCabe C. Whither trial-based economic evaluation for health care decision making? Health Econ. 2006;15:677–87.CrossRefPubMed Sculpher MJ, Claxton K, Drummond M, McCabe C. Whither trial-based economic evaluation for health care decision making? Health Econ. 2006;15:677–87.CrossRefPubMed
Metadata
Title
Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in adult patients with acute lymphoblastic leukemia: clinical outcome and cost-effectiveness analysis
Authors
Yan Wang
Yuanming Xing
Lu Chen
Ti Meng
Ying Li
Jiao Xie
Limei Chen
Yalin Dong
Weihua Dong
Publication date
01-02-2018
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 2/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2342-x

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